Voluntary exercise in mice triggers an anti-osteogenic and pro-tenogenic response in the ankle joint without affecting long bones.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 39493871.
- Also identified by DOI 10.1016/j.bonr.2024.101810 and PMC identifier 11530850.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Biomechanical stimulation is proposed to occupy a central place in joint homeostasis, but the precise contribution of exercise remains elusive. We aimed to characterize in vivo the impact of mechanical stimulation on the cell-controlled regulation of ossification within the ankles of healthy mice undergoing mild physical activity. DBA/1 male mice were subjected to voluntary running exercise for two weeks, and compared to mice housed in standard conditions (<i>n</i> = 20 per group). Free access to activity wheels resulted in a running exercise of 5.5 ± 0.8 km/day at 14.5 ± 0.5 m/min. Serum levels of alkaline phosphatase, IL-6, IL-8/Kc, IL-17a, and TNF-α were measured. No change in systemic inflammation was detected. The bone architecture of the femur and the calcaneus was unchanged, as revealed by μCT and histology of the enthesis of the Achilles tendon. mRNAs were extracted from femurs, tibias, and ankle joints before RT-qPCR analysis. The expression of the mechanosensitive genes <i>Sclerostin</i> (<i>Sost</i>) and <i>Periostin</i> (<i>Postn</i>) was not impacted by the exercise in long bones. Oppositely, <i>Sost</i> and <i>Postn</i> levels were modulated by exercise in joints, and osteogenic markers (<i>Col10a1</i>, <i>Runx2</i>, <i>Osx</i>, and <i>Dmp1</i>) were downregulated in the exercise group. In addition, the tenogenic markers <i>Scx</i>, <i>Mkx</i>, and <i>Tnmd</i> were upregulated by exercise. Thus, voluntary exercise affected the phenotype of joint cells without impacting long bones. As gene expression of <i>Bmp2</i>, <i>Bmp4</i>, and <i>Id1</i> was also reduced in these cells, an off-regulation of BMP signaling could be partly responsible for their mechanosensitive response. Running exercise seemed to preserve the tendon from its progressive ossification, as seen in numerous enthesopathies. This study paves the way to future experiments for investigating the effects of mechanical stimulation in various mouse models.